Genetic variant in Sardinia reduces malaria parasite growth

A new genetic shield against malaria

Scientists have identified a new genetic variant that protects people from malaria. The variant, common in Sardinia, reduces a red blood cell protein's expression and hinders the parasite's ability to grow.

This discovery, published in Nature, adds to a known list of protective genetic traits. Researchers have sought these since the 1940s, when inherited blood disorders were first linked to malaria resistance.

How the protective variant works

The variant affects the gene for a protein called cyclin D3. This protein is crucial for cell division and red blood cell production.

In people with the variant, red blood cells have reduced expression of cyclin D3. This creates an environment where the malaria parasite struggles to replicate effectively.

"This is a possible addition to the set of variants that protect against malaria," the researchers noted. The study suggests the variant was naturally selected in Sardinia due to historical malaria transmission.

The long search for genetic protection

The idea that genetics can shield against malaria is not new. For decades, scientists have studied conditions like sickle cell trait, which offers some protection.

These inherited blood disorders, known as haemoglobinopathies, were first proposed as a defense mechanism in the mid-20th century. Since then, several protective genetic variants have been confirmed.

The new finding is significant because it points to a different biological pathway—cell cycle regulation—as a key factor in resistance.

Why Sardinia holds a clue

The prevalence of this variant in Sardinia's population is a telltale sign of evolutionary pressure. Malaria was historically endemic on the Mediterranean island.

Genetic traits that improve survival in such environments become more common over generations. This process, called positive selection, is why the cyclin D3 variant is found there.

Researchers analyzed genetic data from Sardinians to make the connection between the variant, reduced protein expression, and observed protection.

Implications for future research

Understanding this mechanism opens new avenues for malaria research and potential therapies. Targeting the parasite's lifecycle within red blood cells is a major focus.

The study underscores the complex ways human genetics and infectious diseases interact. Other known genetic defenses against malaria include:

• Sickle cell trait (HbAS)
• Duffy antigen negativity
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency

Each of these affects the parasite's environment or the red blood cell itself in different ways. The cyclin D3 pathway represents a new piece of this puzzle.

A continuing scientific pursuit

The paper, by Marini et al., builds on a long history of investigating host-pathogen evolution. The goal is to translate these natural defenses into medical advances.

While the variant offers protection, it is not absolute. However, studying how it works could inform strategies to mimic its effects.

This research continues to highlight how human populations have genetically adapted to historical disease threats, leaving signatures in our DNA that scientists are still decoding today.